The present invention relates to (1) a novel fluorescent substance produced by substituting a hydrogen atom of the hydroxy group on 3-position of estradiol moiety of a compound synthesized by conjugating estradiol and chlorambucil with a fluorescent material, (2) a process for producing the novel fluorescent substance and (3) a cell-discriminating agent containing the novel fluorescent substance.
Hitherto, trials of conjugating a human hormone and an anticancer medicine, administering the thus prepared compound to a cancer patient, thereby concentrating the anticancer medicine into the specified organ having the receptor of the hormone and attacking the cancer intensively have been carried out.
However, such trials have not exhibited any anticipated effectiveness due to the following reasons.
(1) The specificity of the hormone and/or the anticancer medicine is lost by the conjugation.
(2) Even in the case where the conjugating has been accomplished favorably, since the thus prepared substance attacks both normal and tumor cells, the reduction of the side effect of the antitumor medicine has not been effected to the expected extent.
(3) Because of the unstable bond between the hormone and the antitumor medicine, free antitumor medicine isolates from the conjugated substance and exerts its side effect to the patient.
Formerly, the present inventors have studied the conjugated compound of estradiol and chlorambucil, and have found an unexpected fact that the conjugated compound concentrates onto the tumor cells in a large amount as compared to the normal cells when the hydrogen atom of the hydroxy group on 3-position of estradiol moiety is substituted by an acyl group, more in detail, by acetyl group, propionyl group, butyryl group or benzoyl group, and based on their finding, the present inventors have developed an anticancer medicine having a high anticancer activity and a low side effect.
However, since the precise behavior of the conjugated compounds in a human body, which is necessary for knowing the reason why the conjugated compound concentrates onto the tumor cells at a high concentration, has not been elucidated, it was difficult to further develop the better conjugated compounds along with this idea utilizing the precious and unexpected finding.
Of course, there is a method for observing the behavior of the conjugated compound in a human body by utilizing the radio-labelled conjugated compound, however, the development has not been to the expected extent because of the following reasons;
(1) the radio-labelled, conjugated compound cannot be administered in a large amount to a human body,
(2) it is not easy to prepare the labelled compound, and
(3) determination of radioactivity necessitates an intricated apparatus and complicated procedures.
On this account, as a result of the present inventors' study, it is found that by joining a fluorescent material to the conjugated compound of estradiol and chlorambucil, which make the compound possible to be easily determined and observed by sight, difficult problems how to maintain the property of the conjugated compound to concentrate onto tumor cells in a large amount compared to normal cells have been solved, and based on the finding, the present inventors have attained the present invention.